Method for predicting development of repeated atraumatic intracranial hemorrhage

SUBSTANCE: one should study the level of von Willebrand's factor in patient's carotid artery blood. At its content being below 105% one should predict the development of repeated AICH. The innovation improved information value of testing due to possibility to obtain reliable prediction in latent period, as well.

EFFECT: higher accuracy of prediction.

2 ex, 1 tbl

The invention relates to medicine, namely clinical neurology, neurosurgery, and can be used to predict the development of re nontraumatic intracranial hemorrhage (NBC) in patients in the acute and cold period.

A known method for predicting the development processing using the definition of the level of thrombomodulin blood from a peripheral vein by ELISA. When the concentration of thrombomodulin less 17,3 μg/l predict a high risk of developing NEC (Johansson L., Jansson J. H., Boman, K., Nilsson AS, Stegmayr Century, Hallmans G. Prospective study on soluble thrombomodulin and von Willebrand's factor and the risk of ischemic and hemorrhagic stroke / Thromb. Haemost - 2002 - Vol.87 - P.211-217).

The disadvantage of this method is not accurate because:

- examine the blood from a peripheral vein, changes of hemostatic activity which does not adequately characterize the state of hemostasis in blood vessels of the brain;

- examine the contents of thrombomodulin affecting the activity of coagulation link, and not vascular-platelet, which is primary in the process of stopping the bleeding.

As a prototype of the selected prediction method of re-development processing by determining the radioimmunoassay method in blood from a peripheral vein of thromboxane B2, which is the stable metabolite of thromboxane A2, released from platelets in% the SSE aggregation (Iuwela S.,
Kaste M. Reduced platelet agregability and thromboxane release after rebleeding in patients with subarachnoid hemorrhage / J.Neurosurgery. - 1991. - Vol.74. - P.21-26). When the content of thromboxane B2 in the blood from a peripheral vein in the first 10 days after hemorrhage more 72,7 nmol/l re NBC in the acute period not predict.

The disadvantages of the prototype:

- lack of information, because the method allows to predict the risk of recurrent hemorrhage only in the acute period;

- lack of accuracy, as studied blood from a peripheral vein, changes hemostatically activity which does not adequately characterize the state of hemostasis in blood vessels of the brain.

The invention is directed to a method of predicting the re-development of NBC which would increase the information content by predicting re-NVK as in hot and cold period and increase the accuracy of the method.

This technical result in the implementation of the method is achieved in that in the known method for predicting the re-development of NBC by the quantification of the factors of vascular-platelet hemostasis peculiarity lies in the fact that investigate the level of von Willebrand factor (EF) in the blood from the carotid artery and the content of PE in the carotid artery is less than 105% predict the development of re-processing.

The method is a trail which accordingly.
The patient perform a single blood sample taken from the carotid artery during running angiographic studies in the amount of 4 ml silikonizirovannaya a test tube with 1 ml of 3.8% sodium citrate. The content of the PV is determined by the method of indirect solid-phase enzyme-linked immunosorbent assay (ELISA), the principle of which is as follows: polyclonal antibodies to PV, pre-adsorbed on plastic tablets, interact with their corresponding antigens from the sample, fixing them so on the tablet. Then add the monoclonal antibodies conjugated with horseradish peroxidase enzyme, which, engaging in interaction in molar ratios with a specific substrate, in this case orthophenylphenol leads to staining, on the intensity with which a spectrophotometer is judged on the amount of antigen in the test sample. When the content of PE in blood from the carotid artery is less than 105% predict the development of re-NBC in hot or cold period.

The proposed method for predicting the re-development of NBC developed in SE the Polenov research neurosurgical Institute them. Operated and clinically tested in the survey in 42 patients. The resulting predictions were confirmed by clinical and neurological patterns of disease.

The table presents data on the content of FVU patients depending on the presence of hemorrhage.

Patients without hemorrhagen=22

Patients with repeated bleedingn=20

Contents PV%

145,0±40,4

104,5**±53,7

** p<0,001

As the table shows, the level of PV in the blood from the carotid artery in patients without hemorrhage was significantly higher than in patients with the presence of hemorrhage in the acute or cold period. The reliability of differences Kolmogorov-Smirnov criterion was p<0,001.

Examples of extracts from the histories.

Example 1. Patient M, and a/b No. 2135-2001, with a diagnosis of Arteriovenous malformation deep divisions temporal lobe and parietal lobe on the left. Condition after repeated subarachnoid-parenchymal hemorrhages from 04.2001., 28.07. and 5.08.2001. Angiographic examination, during which the study was carried out according to the claimed method, was conducted 4 months after the three hemorrhages that occurred within 3 months. Level PV 58%, less than 105%, allowed us to predict a high risk of recurrent hemorrhage in the patient, so in a minimally early after studies he performed embolization of arteriovenous malformations, which allowed the predotvratite development hemorrhage in a patient during a two-year follow-up monitoring.

Example 2. Patient P., aged 47, and a/b No. 1047-2001, with a diagnosis of Subarachnoid hemorrhage of unknown etiology from 27.04.01. According to the claimed method were examined in the acute period when performing angiography at 6 days after hemorrhage. Aneurysm angiography is not identified, the level of PV amounted to 208%. When you study after 6 months from the date of hemorrhages detected aneurysm in the rear lower cerebellar artery, and/b No. 2069-01, level PV amounted to 133%. Thus, the level of PV more than 105% in hot and cold period allowed us to predict a low risk of re-bleeding, the patient P., and confirmed by the follow-up period of the disease: in spite of unidentified source of bleeding within 6 months re-NBC was not recorded.

The method allows to increase the information content and predictive accuracy of the re-development of NBC.

A method for predicting the re-development of nontraumatic intracranial hemorrhage by quantifying factors of vascular-platelet hemostasis, characterized in that examine the level of von Willebrand factor in the blood from the carotid artery and when the content is less than 105% predict the development of re nontraumatic intracranial hemorrhage.

SUBSTANCE: one should study both activation and aggregation of thrombocytes in blood of carotid artery, at the quantity of thrombocytic active forms being above 70% and the number of aggregated thrombocytes being above 9.0% one should predict the development of cerebral ischemic lesion along with stable focal neurological symptomatology, and at the quantity of thrombocytic active forms being below 30% and the number of aggregated thrombocytes being below 8.0% it is possible to predict positive dynamics in the course of the disease mentioned without developing cerebral ischemic lesion.

SUBSTANCE: method involves determining coagulating blood viscosity values like reaction period r, thrombin constant K, maximum amplitude MA, time T for forming fibrin-thrombocytic blood clot, spontaneous blood platelets aggregation intensity Ar, retraction and spontaneous clot lysis total FA. The r being within 5-7 min, Ar from -2 to -6 relative units, K being within 4-6 min, MA within 500-700 relative units, T within 40-60 min and FA equal to 10-20%, low inflammatory process activity is considered to be the case. The r being less than 5 min, Ar equal to -8 to -12 relative units, T less than 40 min and FA less than 10% with no changes in K and MA being observed, inflammatory process activity in chronic glomerulonephritis case is considered to be of high severity degree.

SUBSTANCE: the present innovation deals with predicting disadaptive processes in women in dynamics of menstrual cycle. During menstrual cycle beginning since the 1st d to the 21st d one should detect the dynamics for alteration in coefficient of activity of syntoxic adaptation programs (CASAP), calculated by the following formula:

where CST - concentration of blood serotonin, AAT-III - activity of antithrombin III, Aaoa - total antioxidizing activity of plasma, CCD8+ - concentration of T-suppressors, Cad - concentration of blood adrenalin, Cα2MG - concentration of α2-macroglobulin, CMDA - concentration of malonic dialdehyde, CCD4+ - concentration of T-helpers. Moreover, normally CASAP value alters two-fold against the first day of the cycle - since 0.70 up to 1.40 on the 21st d of the cycle, at no alterations in CASAP value one should diagnose female disadaptive alterations leading to failed pregnancy. The innovation enables to perform diagnostics of disadaptive processes in women in dynamics of menstrual cycle followed by prognostic conclusion upon future pregnancy.

SUBSTANCE: one should study blood components to detect anticoagulant-fibrinolytic activity. Moreover, patient's blood should be sampled: in whole blood one should detect the presence of affected erythrocytes and evaluate the quantity of thrombocytes, in plasma it is necessary to study the activity of antithrombin III, XIIa-dependent fibrinolysis, the content of soluble fibrin-monomeric complexes, in blood serum of the sample taken one should detect the concentration of urea, creatinine, sodium, albumin, total cholesterol and the activity of aspartate aminotransferase, moreover, one should calculate integral value of renal-hepatic deficiency, to put corresponding point for the degree of parameters under testing, then one should calculate integral value of disseminated intravascular clotting (IVDIC) and at its value being 6.3 U and more DIC-syndrome should be diagnosed, moreover, at IVDIC value ranged 6.3-10.1 U it is possible to diagnose latent DIC-syndrome, at 10.2-14.6 - subacute DIC-syndrome and at 14.7 and higher - acute DIC-syndrome should be concluded.

SUBSTANCE: one should evaluate the time for clotting of plasma under testing in phospholipid-dependent test, moreover, one should apply high- and low-sensitive thromboplastin reagents to lupus anticoagulant to calculate the ratio of indices of prothrombin time prolongation and at its value being either equal to or above 1.1 one should diagnose APS.

SUBSTANCE: the suggested studying should be carried out on the glass simultaneously with several inductors by applying minimal inter-taking antilogarithms concentrations of aggregation inductors which correspond at double combination of inductors: ADP 5.0 x 10-8 M, adrenaline 3.0 x 10-9, collagen - dissolving the main suspension 1:8, thrombin 0.075 U/ml; at triple combination of inductors: ADP 10-9 M, adrenaline 10-9, collagen - dissolving the main suspension 1:9, thrombin 0.060 U/ml. The development of aggregation means thrombocytic activation in patients with arterial hypertension at metabolic syndrome. The method enables to evaluate the changes of thrombocytic functional state with combination of inductors more probably present in area of vascular lesion by applying minimal necessary concentrations that develops real conditions at hemostatic initiation in human vessels.

SUBSTANCE: the suggested studying should be carried out on the glass simultaneously with several inductors by applying minimal inter-taking antilogarithms concentrations of aggregation inductors which correspond at double combination of inductors: ADP 5.0 x 10-8 M, adrenaline 3.0 x 10-9, collagen - dissolving the main suspension 1:8, thrombin 0.075 U/ml; at triple combination of inductors: ADP 10-9 M, adrenaline 10-9, collagen - dissolving the main suspension 1:9, thrombin 0.060 U/ml. The development of aggregation means thrombocytic activation in patients with arterial hypertension at metabolic syndrome. The method enables to evaluate the changes of thrombocytic functional state with combination of inductors more probably present in area of vascular lesion by applying minimal necessary concentrations that develops real conditions at hemostatic initiation in human vessels.

SUBSTANCE: one should evaluate the time for clotting of plasma under testing in phospholipid-dependent test, moreover, one should apply high- and low-sensitive thromboplastin reagents to lupus anticoagulant to calculate the ratio of indices of prothrombin time prolongation and at its value being either equal to or above 1.1 one should diagnose APS.

SUBSTANCE: one should study blood components to detect anticoagulant-fibrinolytic activity. Moreover, patient's blood should be sampled: in whole blood one should detect the presence of affected erythrocytes and evaluate the quantity of thrombocytes, in plasma it is necessary to study the activity of antithrombin III, XIIa-dependent fibrinolysis, the content of soluble fibrin-monomeric complexes, in blood serum of the sample taken one should detect the concentration of urea, creatinine, sodium, albumin, total cholesterol and the activity of aspartate aminotransferase, moreover, one should calculate integral value of renal-hepatic deficiency, to put corresponding point for the degree of parameters under testing, then one should calculate integral value of disseminated intravascular clotting (IVDIC) and at its value being 6.3 U and more DIC-syndrome should be diagnosed, moreover, at IVDIC value ranged 6.3-10.1 U it is possible to diagnose latent DIC-syndrome, at 10.2-14.6 - subacute DIC-syndrome and at 14.7 and higher - acute DIC-syndrome should be concluded.

SUBSTANCE: the present innovation deals with predicting disadaptive processes in women in dynamics of menstrual cycle. During menstrual cycle beginning since the 1st d to the 21st d one should detect the dynamics for alteration in coefficient of activity of syntoxic adaptation programs (CASAP), calculated by the following formula:

where CST - concentration of blood serotonin, AAT-III - activity of antithrombin III, Aaoa - total antioxidizing activity of plasma, CCD8+ - concentration of T-suppressors, Cad - concentration of blood adrenalin, Cα2MG - concentration of α2-macroglobulin, CMDA - concentration of malonic dialdehyde, CCD4+ - concentration of T-helpers. Moreover, normally CASAP value alters two-fold against the first day of the cycle - since 0.70 up to 1.40 on the 21st d of the cycle, at no alterations in CASAP value one should diagnose female disadaptive alterations leading to failed pregnancy. The innovation enables to perform diagnostics of disadaptive processes in women in dynamics of menstrual cycle followed by prognostic conclusion upon future pregnancy.

SUBSTANCE: method involves determining coagulating blood viscosity values like reaction period r, thrombin constant K, maximum amplitude MA, time T for forming fibrin-thrombocytic blood clot, spontaneous blood platelets aggregation intensity Ar, retraction and spontaneous clot lysis total FA. The r being within 5-7 min, Ar from -2 to -6 relative units, K being within 4-6 min, MA within 500-700 relative units, T within 40-60 min and FA equal to 10-20%, low inflammatory process activity is considered to be the case. The r being less than 5 min, Ar equal to -8 to -12 relative units, T less than 40 min and FA less than 10% with no changes in K and MA being observed, inflammatory process activity in chronic glomerulonephritis case is considered to be of high severity degree.

SUBSTANCE: one should study both activation and aggregation of thrombocytes in blood of carotid artery, at the quantity of thrombocytic active forms being above 70% and the number of aggregated thrombocytes being above 9.0% one should predict the development of cerebral ischemic lesion along with stable focal neurological symptomatology, and at the quantity of thrombocytic active forms being below 30% and the number of aggregated thrombocytes being below 8.0% it is possible to predict positive dynamics in the course of the disease mentioned without developing cerebral ischemic lesion.

SUBSTANCE: one should study the level of von Willebrand's factor in patient's carotid artery blood. At its content being below 105% one should predict the development of repeated AICH. The innovation improved information value of testing due to possibility to obtain reliable prediction in latent period, as well.